Estradiol-17β and progesterone fluctuate during the menstrual cycle, and they have multiple effects that can be categorized according to whether they are directly related to the reproductive system or not. Both hormones have profound effects on the ovary, oviduct, uterus, cervix, vagina, and external genitalia and on the hypothalamus and pituitary. Estrogen and progesterone also have important effects on nonreproductive tissues: Bone: Estrogen is required for closure of the epiphyseal plates of long bones in both sexes. Estradiol-17β has a bone anabolic and calciotropic effect (see ). It stimulates intestinal Ca++ absorption. Estradiol-17β is also one of the most potent regulators of osteoblast and osteoclast function. Estrogen promotes survival of osteoblasts and apoptosis of osteoclasts, thereby favoring bone formation over resorption. Low estrogen levels associated with menopause leads to bone loss and osteoporosis.
Liver: The overall effect of estradiol-17β on the liver is to improve circulating lipoprotein profiles. Estrogen increases expression of the LDL receptor, thereby increasing clearance of cholesterol-rich LDL particles by the liver. Estrogen also increases circulating levels of HDL. Estrogen regulates hepatic production of several transport proteins, including cortisol-binding protein, thyroid hormone–binding protein, and SHBG.
CHAPTER 44 The Male and Female Reproductive Systems
Cardiovascular organs: Premenopausal women have significantly less cardiovascular disease than men or post-menopausal women do. Estrogen promotes vasodilation through increased production of nitric oxide, which relaxes vascular smooth muscle and inhibits platelet activation. Single-nucleotide polymorphisms in the estrogen receptor have been associated with increased cardiovascular disease.
Integument: Estrogen and progesterone maintain healthy smooth skin with normal epidermal and dermal thickness. Estrogen stimulates proliferation and inhibits apoptosis of keratinocytes. In the dermis, estrogen and progesterone increase collagen synthesis and inhibit breakdown of collagen by suppressing matrix metalloproteinases. Estrogen also increases glycosaminoglycan production and deposition in the dermis and promotes wound healing.
CNS: Estrogen is neuroprotective—that is, it inhibits neuronal cell death in response to hypoxia or other insults. Estrogen’s positive effects on angiogenesis may account for some of the beneficial and stimulant-like actions of estrogen on the CNS. Progesterone acts on the hypothalamus to increase the set point for thermoregulation, thereby elevating body temperature approximately 0.5°F. This is the basis for using body temperature measurements to determine whether ovulation has occurred. Progesterone is a CNS depressant. Loss of progesterone on demise of the corpus luteum of menstruation is the basis for premenstrual dysphoria (premenstrual syndrome [PMS]). Progesterone also acts on the brainstem to sensitize the ventilatory response to PCO2 so that ventilation increases and PCO2 decreases.
Adipose tissue: Estrogen decreases adipose tissue by decreasing lipoprotein lipase activity and increasing hormone-sensitive lipase (i.e., it has a lipolytic effect). Loss of estrogen results in accumulation of adipose tissue, especially in the abdomen.
Transport and Metabolism of Ovarian Steroids